Neuroprotective effects of melatonin against neurotoxicity induced by intranasal sodium dimethyldithiocarbamate administration in mice.

Abstract

Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson's disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now investigated the putative neuroprotective effects of melatonin on behavioral dificits and neurochemical alterations induced by i.n. NaDMDC. Melatonin treatment (3, 10 or 30 mg/kg, i.p.) was given 1 h before NaDMDC administration (1 mg/nostril) during 4 consecutive days and we evaluated early (up to 7 days) and late (up to 35 days) NaDMDC-induced behavioral and neurochemical alterations. Melatonin treatment protected against early motor and general neurological impairments observed in the open field and neurological score of severity, respectively, and late deficits in rotarod test. Melatonin prevented the NaDMDC-induced alterations in the striatal tyrosine hydroxylase immunocontent. Melatonin also protected against increased levels of oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine) in the striatum, as well as the NaDMDC-induced increase of 4-hydroxynonenal and TNF, markers of oxidative stress and inflammation, respectively, in the olfactory bulb. These results further detail the mechanisms underlying NaDMDC toxicity and demonstrate the neuroprotective effects of melatonin against the neuronal damage induced by NaDMDC.

• Authors: Josiel Mileno Mack, Tainara de Menezes Moura, Franciane Bobinski, Daniel Fernandes Martins, Rodrigo A Cunha, Roger Walz, Pedro Augusto Fernandes, Regina Pekelmann Markus, Alcir Luiz Dafre, Rui Daniel Prediger
• Journal: Neurotoxicology (Neurotoxicology) Vol. 80 Pg. 144-154 (09 2020) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 32738267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Dimethyldithiocarbamate
• Neuroprotective Agents
• Melatonin

Topics

• Administration, Intranasal
• Animals
• Behavior, Animal (drug effects)
• Brain (drug effects, metabolism, physiopathology)
• Dimethyldithiocarbamate
• Disease Models, Animal
• Dopaminergic Neurons (drug effects, metabolism, pathology)
• Male
• Melatonin (pharmacology)
• Mice
• Motor Activity (drug effects)
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (etiology, metabolism, physiopathology, prevention & control)
• Nitrosative Stress (drug effects)
• Oxidative Stress (drug effects)